Genome Russia project - Analyses Progress and Update

Stephen J. OBrien * and the Genome Russia Consortium of Scientists

Chief Scientific Officer, Theodosius Dobzhansky Center for Genome Bioinformatics St. Petersburg State University

We are witnessing the great era of genome exploration of the world, as genetic variation in people is being detailed across multiple varied world populations in an effort unprecedented since the first human genome sequence appeared in 2001. However, these efforts have yet to produce a comprehensive mapping of humankind, because important regions of modern human civilization remain unexplored. The Genome Russia Project, initiated in early 2015, promises to fill one of the largest gaps, the expansive regions across the Russian Federation, informing not just medical genomics of the territories, but also the migration settlements of historic and pre-historic Eurasian peoples. I shall outline the progress and challenges in Project implementation, execution in sequence acquisition, genome annotation, mutation discovery and mining, database development , HapMap construction, Phylogeography and data release to the world-wide genomics communities.

Stephen J. O’Brien

Stephen J. O’Brien served as Chief of the Laboratory of Genomic Diversity at the National Cancer Institute (NCI), National Institutes of Health (NIH) from 1986-2011.

In December 2011, he joined the Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University as Chief Scientific Officer. http://dobzhanskycenter.bio.spbu.ru/?lang=en.

In January 2013, he joined the Faculty as Professor at the Oceanographic Center, Nova Southeastern University Ft Lauderdale FL. http://www.nova.edu/ocean/overview/faculty-staff-profiles/stephen_james_obrien.html

Stephen J. O’Brien earned his Ph.D in genetics at Cornell where he expanded the nascent discipline of biochemical genetics, developing the gene-enzyme maps of Drosophila melanogaster. His biochemical mapping would stimulate his editing of six editions of Genetic Maps: Locus Maps of Complex Genomes (1980-1993) (Cold Spring Harbor Laboratory Publications), international unabridged compendiums of plant, animal, bacteria and virus genetic maps that were prelude to the online NCBI gene mapping databases of species whole genome DNA sequences.

O’Brien is known for his research contributions in comparative genomics, virology, genetic epidemiology, mammalian systematics and species conservation.

In 1983, he and his collaborators discovered the remarkable genetic uniformity of the African cheetah, a prelude to a new discipline of Conservation Genetics. Over three decades of filed studies with his students and colleagues, he subsequently reported over 300 publications, many in the highest rated scientific journals of how genetics could inform and facilitate management action for endangered species. These included identifying new species of elephant, clouded leopard and orangutan plus detailed genetics studies on threatened wildlife species including cheetahs, lions, tigers, giant panda, leopards, pumas, jaguars, koalas, humpback whales .

In 1982, O’Brien’s team at the NIH published a comprehensive gene map of domestic cat as cover article in SCIENCE and compared genome organization of the cat to human, mouse and other species demonstrating extreme conservation of chromosomal synteny (homologous gene order) between disparate mammalian species . These and subsequent studies (circa 250 publication; many in leading journals ) established the field of Comparative Genomics. This discipline today remains a baseline for interpreting the organization and evolution of human and established the domestic cat as a powerful genetic model for hereditary cancer and infections diseases in man and animals.

In 1996 O’Brien’s team described he first human gene to influence HIV-1 infection and AIDS progression, CCR5-Δ32, using population genetic based association analysis. This discovery has led to several HIV entry inhibitor developments that have been approved by FDA as also stimulated the first real cure of HIV-AIDS in the so called Berlin patient who permanently cleared HIV when infused with CCR5-Δ32/CCR5-Δ32 donor stem cells in 2006. O’Brien’s group used similar genetic association studies to invigorate the field of Genetic Epidemiology, describing over 30 AIDS restriction genes and also applying these gene discovery strategies to chronic infectious human diseases including, hepatitis c, hepatitis, HBV hepatocellular carcinoma, and nasopharyngeal carcinoma.

In 2009 O’Brien joined with David Haussler and Oliver Ryder to found the Genome10K project, an international consortium of genome scientists joined together to facilitate the whole genome sequencing, assembly and annotation of 10,000 vertebrate species by 2015. (http://genome10k.org/) Proposed through breakpoint parsimony the: Dr. O’Brien has a strong dedication to education, evidenced by his appointments as adjunct professor at twelve universities: Harvard University, The Johns Hopkins University, Cornell University, Duke University, Peking University-Beijing, University of Maryland, University of Minnesota, Michigan State University, Colorado State University, George Washington University, George Mason University, and Hood College of Frederick. He has mentored more than fifteen Ph.D. students including: Roger Reeves, Dennis Gilbert, Robert Wayne, Cheryl Winkler, Jose Lopez, Melanie Culver, Eduardo Eizirik, Olga Uphyrkina, Carlos Driscoll, Meredith Brown, and Shu Jin Luo in addition to eight M.S. theses and over thirty post-doctoral fellows. Since 1996 he has directed an internationally heralded short course sponsored by Smithsonian and American Genetics Association, entitled “Recent Advances in Conservation Genetics”, the most recent (2009) edition at The Smithsonian Tropical Research Institute ,in Panama.

Dr. O’Brien was elected to the American Academy of Arts and Science, to the Explorer’s Club, and to the Cosmos Club . He served as President of the NIH Assembly of Scientists, as Chairman of the International Committee on Comparative Gene Mapping for the Human Genome Organization (HUGO). Dr. O’Brien founded and co-directs NOAHS (New Opportunities in Animal Health Sciences), a consortium of scientists and apprentices, part of the Smithsonian Institution/National Zoological Park, dedicated to applying biomedical technology on behalf of species conservation and to training a generation of conservation scientists. He is presently the Chairman of the Science Advisory Board for The International BarCode of Life Project ( http://ibol.org/) and Chairman of the Board of the Cheetah Conservation Fund (http://www.cheetah.org/)

Dr. O’Brien is the author or co-author of over 800 scientific articles and the editor of fourteen volumes. In 2004 he published a popular book of science adventure stories entitled “Tears of the Cheetah And Other Tales From The Genetic Frontier” (St. Martin’s Pres NYC); in 2007, he published a comprehensive “Atlas of Mammalian Chromosomes” , a photo-compendium of the karyotype of nearly 1000 species of mammals, (John Wiley Inc. NYC). Dr. O’Brien has served as editor of six editions of Genetic Maps: Locus Maps of Complex Genomes (Cold Spring Harbor Laboratory Press); Editor of Journal of Heredity (American Genetics Association) from 1987-2007; Editor for Isozyme Bulletin; Associate Editor for Genomics; Human Genomics, Mammalian Genome, Molecular Phylogenetics and Evolution, and Cosmos.

Dr. O’Brien received his B.S. in Biology in 1966 from St. Francis College, which presented him with a Distinguished Alumni Award in 1994. In 1971 he earned a Ph.D. in Genetics from Cornell University which honored him as “Andrew Dixon White Endowed Professor at Large” in 1998. In 2009, he was awarded an honorary Doctorate of Veterinary Medicine from the University of Zurich.